Identification of nucleic acids can be useful for several applications, including analysis of gene expression, genome analysis for clinical diagnosis, biomedical research, forensic investigations, and biometrics. In a conventional approach, one assay format is based on hybridization of target nucleic acids that are fluorescently-labeled with complementary probes that are bound to a solid surface. For example, using a set of 14 to 40 complementary probes, each probe containing 25 nucleotides, it is possible to classify single nucleotide polymorphisms (SNPs).
Another conventional approach for classifying nucleic acids is based on divergent sequences. For example, the classifying nucleic acids can include hybridization of target nucleic acid with capture probes on particulates. The hybrid can include an oligonucleotide sequence that is immediately adjacent to a polymorphic site. The hybrid can be extended by polymerase to incorporate the nucleotide that appropriately pairs with the polymorphic nucleotide. The incorporation of the nucleotide results in chain termination. The compound is marked with a fluorescent label and spectral analysis can provide the identity of the nucleotide.
Long, closely related alleles appear in human genomic DNA. The ability of conventional approaches to distinguish variants of long, closely related genetic sequences that contain short tandem repeats (STRs) that vary in length is limited. Conventional approaches of nucleic acid identification often require long equilibration times, and are limited by high background signal and low dynamic range.